title: Plasmodium falciparum antigen-induced human immunodeficiency virus type 1 replication is mediated through induction of tumor necrosis factor-alpha.
abstract: Because malaria-stimulated cytokine production may have deleterious effects on human immunodeficiency virus type 1 (HIV-1) replication, the effects of Plasmodium falciparum antigens on HIV-1 replication were studied. Stimulation with malarial antigens significantly enhanced HIV-1 replication of HIV-1LAV and primary HIV-1 isolates (subtype A) in CD8-depleted peripheral blood mononuclear cells from naive donors. The malarial antigen-induced activation of HIV-1 was due to cellular activation as judged by the expression of cell activation markers and proliferative responses. While malarial antigen stimulation increased expression of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6), only monoclonal antibodies (MAbs) to TNF-alpha inhibited malarial antigen-induced HIV-1 replication, whereas MAb to IL-6 had no effect. Malarial antigen increased HIV-1 replication by increasing viral mRNA expression and by activating long terminal repeat-directed viral transcription. These data suggest that P. falciparum infection can modulate HIV-1 pathogenesis by activating lymphocytes and stimulating viral replication through the production of cytokines.
authors.affiliation: Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.forename: S M
authors.initials: SM
authors.lastname: Owen
authors.forename: D L
authors.initials: DL
authors.lastname: Rudolph
authors.forename: R B
authors.initials: RB
authors.lastname: Lal
authors.forename: A A
authors.initials: AA
authors.lastname: Lal
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000276:immunology; D015497:HIV-1; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008213:Lymphocyte Activation; D010963:Plasmodium falciparum / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D000953:Antigens, Protozoan; D016655:HIV Core Protein p24; D006684:HLA-DR Antigens; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10